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Title: Induction of tolerance to cardiac allografts in lethally irradiated rats reconstituted with syngeneic bone marrow

Abstract

Generally, organ grafts from one individual animal to another are rejected in one-two weeks. However, if the recipients are given Total Body Irradiation (TBI) just prior to grafting, followed by reconstitution of hemopoietic function with syngeneic (recipient-type) bone marrow cells, then vascularized organ grafts are permanently accepted. Initially after irradiation, it is possible to induce tolerance to many strain combinations in rats. This thesis examines the system of TBI as applied to the induction of tolerance in LEW recipients of WF cardiac allografts. These two rat strains are mismatched across the entire major histocompatibility complex. When the LEW recipient are given 860 rads, a WF cardiac allograft and LEW bone marrow on the same day, 60% of the grafts are accepted. Methods employed to improve the rate of graft acceptance include: treating either donor or recipient with small amounts of methotrexate, or waiting until two days after irradiation to repopulate with bone marrow. It seems from these investigations of some of the early events in the induction of tolerance to allografts following TBI and syngeneic marrow reconstitution that an immature cell population in the bone marrow interacts with a radioresistant cell population in the spleen to produce tolerance to completelymore » MHC-mismatched allografts.« less

Authors:
Publication Date:
Research Org.:
Boston Univ., MA (USA). Graduate School
OSTI Identifier:
5802235
Resource Type:
Thesis/Dissertation
Resource Relation:
Other Information: Thesis (Ph. D.)
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; IMMUNOSUPPRESSION; RADIOINDUCTION; RATS; BIOLOGICAL RADIATION EFFECTS; RADIOIMMUNOLOGY; BONE MARROW; GRAFTS; LETHAL IRRADIATION; SPLEEN CELLS; WHOLE-BODY IRRADIATION; ANIMAL CELLS; ANIMAL TISSUES; ANIMALS; BIOLOGICAL EFFECTS; BODY; EXTERNAL IRRADIATION; HEMATOPOIETIC SYSTEM; IMMUNOLOGY; IRRADIATION; MAMMALS; ORGANS; RADIATION EFFECTS; RODENTS; SOMATIC CELLS; TISSUES; TRANSPLANTS; VERTEBRATES; 560152* - Radiation Effects on Animals- Animals

Citation Formats

Hartnett, L.C. Induction of tolerance to cardiac allografts in lethally irradiated rats reconstituted with syngeneic bone marrow. United States: N. p., 1983. Web.
Hartnett, L.C. Induction of tolerance to cardiac allografts in lethally irradiated rats reconstituted with syngeneic bone marrow. United States.
Hartnett, L.C. Sat . "Induction of tolerance to cardiac allografts in lethally irradiated rats reconstituted with syngeneic bone marrow". United States. doi:.
@article{osti_5802235,
title = {Induction of tolerance to cardiac allografts in lethally irradiated rats reconstituted with syngeneic bone marrow},
author = {Hartnett, L.C.},
abstractNote = {Generally, organ grafts from one individual animal to another are rejected in one-two weeks. However, if the recipients are given Total Body Irradiation (TBI) just prior to grafting, followed by reconstitution of hemopoietic function with syngeneic (recipient-type) bone marrow cells, then vascularized organ grafts are permanently accepted. Initially after irradiation, it is possible to induce tolerance to many strain combinations in rats. This thesis examines the system of TBI as applied to the induction of tolerance in LEW recipients of WF cardiac allografts. These two rat strains are mismatched across the entire major histocompatibility complex. When the LEW recipient are given 860 rads, a WF cardiac allograft and LEW bone marrow on the same day, 60% of the grafts are accepted. Methods employed to improve the rate of graft acceptance include: treating either donor or recipient with small amounts of methotrexate, or waiting until two days after irradiation to repopulate with bone marrow. It seems from these investigations of some of the early events in the induction of tolerance to allografts following TBI and syngeneic marrow reconstitution that an immature cell population in the bone marrow interacts with a radioresistant cell population in the spleen to produce tolerance to completely MHC-mismatched allografts.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Sat Jan 01 00:00:00 EST 1983},
month = {Sat Jan 01 00:00:00 EST 1983}
}

Thesis/Dissertation:
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  • Total body irradiation and repopulation with syngeneic hemopoietic cells can be used to induce tolerance to major histocompatibility complex (MHC) mismatched heart and kidney grafts in rats and mice. However, this protocol does not work for MHC mismatched skin grafts in rats or mice. Furthermore, LEW rats that accept WF cardiac allografts after irradiation and repopulation reject subsequent WF skin grafts. Treatment of skin allograft donors with methotrexate prior to grafting onto irradiated and reconstituted mice resulted in doubling of the mean survival time. Analysis of which antigens provoked skin graft rejection by irradiation and reconstituted animals revealed the importancemore » of I region antigens. Cardiac allograft acceptance by irradiated and reconstituted animals is mediated by suppressor cells found in the spleen. Adoptively tolerant LEW rats accepted WF skin grafts in 50% of grafted animals. Analysis of this phenomenon revealed that the adoptive transfer procedure itself was important in achieving skin allograft acceptance by these animals. In general, it seems that the lack of ability of irradiated and reconstituted animals to accept fully MHC disparate skin grafts results from the inability of these animals to suppress lymph node effector cells against I region antigen seen on highly immunogenic allogeneic Langerhans cells in the skin.« less
  • It is generally agreed that most, if not all, technical problems of cardiac transplantation in experimental animals and in human subjects have been mastered. Successful application of this technique to the treatment of end-stage cardiac disease continues to be hampered, however, by the host's reaction to a cardiac allograft as foreign tissue, and his attempt to destroy such tissue by immunological reactions normally implicated in defense mechanisms against infectious microorganisms. Earlier studies in this laboratory have demonstrated that DL-A compatibility can exert a potent influence on the survival of orthotopic cardiac allografts in the unmodified canine host. The present reportmore » demonstrates that supralethal total body irradiation and bone marrow transplantation from a genotypically DL-A identical donor can induce in canine recipients an immunologically specific state of unresponsiveness to an orthotopic heart transplant obtained from the marrow donor.« less